title: Inhibition of ADP-ribosylation suppresses aberrant accumulation of lipidated apolipoprotein B in the endoplasmic reticulum.
abstract: ApoB-crescent, an endoplasmic reticulum (ER)-lipid droplet amalgamation structure, is a useful marker to indicate aberrant lipidated apolipoprotein B accumulation in the hepatocyte ER. Blockade of the ER-to-Golgi transport by either vesicle transport inhibitors or dominant-negative Arf1 caused a significant increase in ApoB-crescents. However, a low concentration of Brefeldin A induced the same result without affecting protein secretion, suggesting ADP-ribosylation as an additional mechanism. ADP-ribosylation inhibitors not only suppressed the increase of ApoB-crescents, but also rapidly dissolved existing ApoB-crescents. These results implicate the involvement of ADP-ribosylation in the ApoB-crescent formation and maintenance process at the ER.
authors.affiliation: Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ohsaki
authors.forename: Jinglei
authors.initials: J
authors.lastname: Cheng
authors.forename: Kazushi
authors.initials: K
authors.lastname: Yamairi
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Pan
authors.forename: M Mahmood
authors.initials: MM
authors.lastname: Hussain
authors.forename: Toyoshi
authors.initials: T
authors.lastname: Fujimoto
mesh_terms: D019797:3-Iodobenzylguanidine / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D001055:Apolipoproteins B / Q000378:metabolism*; D020126:Brefeldin A / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D054878:Lipoylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D021381:Protein Transport / Q000187:drug effects
chemical_list: D001055:Apolipoproteins B; D002352:Carrier Proteins; C106092:microsomal triglyceride transfer protein; D020126:Brefeldin A; D000246:Adenosine Diphosphate Ribose; D019797:3-Iodobenzylguanidine
keywords: 4,6-diamidino-2-phenylindole; ADP; ADP-ribosylation; ADP-ribosylation factor 1; ALLN; ApoB; ApoB-crescent; Arf1; BFA; Brefeldin A; DAPI; DHA; ER; GDP; GEF; GTP; LD; LPDS; Lipid droplet; MIBG; MTP; N-acetyl-l-leucyl-l-leucyl-l-norleucinal; NAM; NDGA; OA; VLDL; adenosine diphosphate; apolipoprotein B-100; brefeldin A; docosahexaenoic acid; endoplasmic reticulum; guanine diphosphate; guanine nucleotide exchange factor; guanine triphosphate; lipid droplet; lipoprotein deficient serum; m-iodobenzylguanidine hemisulfate salt; microsomal triglyceride transfer protein; nicotinamide; nordihydroguaiaretic acid; oleic acid; very low-density lipoprotein